Many studies have examined the negative effects of work-family conflict on society, organizations, and individuals. Nonetheless, alleviating employee work-family conflict is a topic worthy of further investigation. Few studies examine the antecedent variables of work-family conflict from personal skill and Guanxi perspectives. Studies that test the moderating role of family-friendly practices at the organization level are also rare. Accordingly, we collected data from 404 employees of 51 organizations. The research data are time-lagged and multileveled. The results of hierarchical linear model (HLM) show: (1) Employee political skill negatively affects employee perceived work-family conflict; (2) Employee political skill positively affects supervisor-subordinate Guanxi; (3) Supervisor-subordinate Guanxi partially mediates the relationship between employee political skill and employee work-family conflict (that is, employees can use their political skill to build high-quality supervisor-subordinate Guanxi, further reducing their perceived work-family conflict); (4) Organization family-friendly practices negatively moderate the relationship between supervisor-subordinate Guanxi and work-family conflict (that is, in organizations with high level family-friendly practices, the negative relationship between supervisor-subordinate Guanxi and work-family conflict becomes weak); Furthermore, by coding with Mplus software (Muthen & Muthen, Los Angeles, CA, USA), we also find: (5) Organization family-friendly practices moderate the indirect effect of employee political skill on employee work-family conflict. The results have both theoretical and empirical implications. Further research directions are addressed at the end.